摘要
An overview of about 70-year research efforts in area of mathematical modeling of human physiology is provided.The overview has two goals:(1)to recognize the main advantages and causes of disadvantages or disappointments;(2)to distinguish the most promising approach for creating future models.Until recently,efforts in the modeling of quantitative physiology were concentrated on the solving of three main types of tasks:(1)how to establish the input-output dynamic characteristics of a given isolated organ or isolated anatomical-functional system(AFS);(2)how to create a computer-based simulator of physiological complex systems(PCM)containing many organs and AFSs;and(3)how to create multi-scale models capable of simulating and explaining causalities in organs,AFSs,PCMs,and in the entire organism in terms that will allow using such models for simulating pathological scenarios(the“Physiome”project)too.The critical analysis of the modeling experience and recent physiological concepts convinced us that the platform provided by the paradigm of physiological super-systems(PPS)looks like the most promising platform for further modeling.PPS causally combines activities of specific intracellular mechanisms(self-tunable but of limited capacities)with their extracellular enhancers.The enhancement appears due to the increase of nutrients incomes toward cells affected because of low energy and inadequate chemical composition of cytoplasm.Every enhancer has its activator chemicals released by the affected cells.In fact,PPS,indicating causal relationships between cellscale and upper-scales(in organs,AFSs,PCMs)physiological activities,is the single platform for future models.They must definitely describe when and how the bottom-to-up information flows do appear and how is the organism-scale adaptation activated against destructive trends in cells.
